University of Central Florida, Orlando.
IEEE/ACM Trans Comput Biol Bioinform. 2012 Jan-Feb;9(1):1-11. doi: 10.1109/TCBB.2011.86. Epub 2011 Apr 29.
Structure-based RNA multiple alignment is particularly challenging because covarying mutations make sequence information alone insufficient. Existing tools for RNA multiple alignment first generate pairwise RNA structure alignments and then build the multiple alignment using only sequence information. Here we present PMFastR, an algorithm which iteratively uses a sequence-structure alignment procedure to build a structure-based RNA multiple alignment from one sequence with known structure and a database of sequences from the same family. PMFastR also has low memory consumption allowing for the alignment of large sequences such as 16S and 23S rRNA. The algorithm also provides a method to utilize a multicore environment. We present results on benchmark data sets from BRAliBase, which shows PMFastR performs comparably to other state-of-the-art programs. Finally, we regenerate 607 Rfam seed alignments and show that our automated process creates multiple alignments similar to the manually curated Rfam seed alignments. Thus, the techniques presented in this paper allow for the generation of multiple alignments using sequence-structure guidance, while limiting memory consumption. As a result, multiple alignments of long RNA sequences, such as 16S and 23S rRNAs, can easily be generated locally on a personal computer. The software and supplementary data are available at http://genome.ucf.edu/PMFastR.
基于结构的 RNA 多重比对特别具有挑战性，因为共变突变使得仅序列信息不够。现有的 RNA 多重比对工具首先生成两两 RNA 结构比对，然后仅使用序列信息构建多重比对。在这里，我们介绍了 PMFastR，这是一种算法，它通过使用序列-结构比对过程从具有已知结构的一个序列和来自同一家族的序列数据库中构建基于结构的 RNA 多重比对。PMFastR 还具有低内存消耗，允许对大型序列（如 16S 和 23S rRNA）进行比对。该算法还提供了一种利用多核环境的方法。我们在 BRAliBase 的基准数据集上展示了结果，表明 PMFastR 与其他最先进的程序表现相当。最后，我们重新生成了 607 个 Rfam 种子比对，并表明我们的自动化过程创建的多重比对与人工 curated 的 Rfam 种子比对相似。因此，本文提出的技术允许使用序列-结构指导生成多重比对，同时限制内存消耗。结果，长 RNA 序列（如 16S 和 23S rRNA）的多重比对可以很容易地在个人计算机上本地生成。软件和补充数据可在 http://genome.ucf.edu/PMFastR 获得。
